Showing papers by "University of Tsukuba published in 2018"

Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Social robots for education: A review

Abstract: Social robots can be used in education as tutors or peer learners. They have been shown to be effective at increasing cognitive and affective outcomes and have achieved outcomes similar to those of human tutoring on restricted tasks. This is largely because of their physical presence, which traditional learning technologies lack. We review the potential of social robots in education, discuss the technical challenges, and consider how the robot's appearance and behavior affect learning outcomes.

Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos).

Abstract: Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Emerging roles of long non-coding RNA in cancer.

Abstract: Since comprehensive analysis of the mammalian genome revealed that the majority of genomic products are transcribed in long non-coding RNA (lncRNA), increasing attention has been paid to these transcripts. The applied next-generation sequencing technologies have provided accumulating evidence of dysregulated lncRNA in cancer. The implication of this finding can be seen in many forms and at multiple levels. With impacts ranging from integrating chromatin remodeling complexes to regulating transcription and post-transcriptional processes, aberrant expression of lncRNA may have repercussions in cell proliferation, tumor progression or metastasis. lncRNA may act as enhancers, scaffolds or decoys by physically interacting with other RNA species or proteins, resulting in a direct impact on cell signaling cascades. Even though their functional classification is well-established in the context of cancer, clearer characterization in terms of their phenotypic outputs is needed to optimize and identify suitable candidates that enable the development of new therapeutic strategies and the design of novel diagnostic approaches. The present article aims to outline different cancer-associated lncRNA according to their contribution to tumor suppression or tumor promotion based on their most current functional annotations.

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

Abstract: We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

Search for dark matter and other new phenomena in events with an energetic jet and large missing transverse momentum using the ATLAS detector

Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses proton-proton collision data corresponding to an integrated luminosity of 36.1 fb−1 at a centre-of-mass energy of 13 TeV collected in 2015 and 2016 with the ATLAS detector at the Large Hadron Collider. Events are required to have at least one jet with a transverse momentum above 250 GeV and no leptons (e or μ). Several signal regions are considered with increasing requirements on the missing transverse momentum above 250 GeV. Good agreement is observed between the number of events in data and Standard Model predictions. The results are translated into exclusion limits in models with pair-produced weakly interacting dark-matter candidates, large extra spatial dimensions, and supersymmetric particles in several compressed scenarios.

A small peptide modulates stomatal control via abscisic acid in long-distance signalling

Abstract: Mammalian peptide hormones propagate extracellular stimuli from sensing tissues to appropriate targets to achieve optimal growth maintenance 1 . In land plants, root-to-shoot signalling is important to prevent water loss by transpiration and to adapt to water-deficient conditions2, 3. The phytohormone abscisic acid has a role in the regulation of stomatal movement to prevent water loss 4 . However, no mobile signalling molecules have yet been identified that can trigger abscisic acid accumulation in leaves. Here we show that the CLAVATA3/EMBRYO-SURROUNDING REGION-RELATED 25 (CLE25) peptide transmits water-deficiency signals through vascular tissues in Arabidopsis, and affects abscisic acid biosynthesis and stomatal control of transpiration in association with BARELY ANY MERISTEM (BAM) receptors in leaves. The CLE25 gene is expressed in vascular tissues and enhanced in roots in response to dehydration stress. The root-derived CLE25 peptide moves from the roots to the leaves, where it induces stomatal closure by modulating abscisic acid accumulation and thereby enhances resistance to dehydration stress. BAM receptors are required for the CLE25 peptide-induced dehydration stress response in leaves, and the CLE25–BAM module therefore probably functions as one of the signalling molecules for long-distance signalling in the dehydration response.

Direct Visualization of the Reversible O2- /O- Redox Process in Li-Rich Cathode Materials.

Abstract: Conventional cathodes of Li-ion batteries mainly operate through an insertion-extraction process involving transition metal redox. These cathodes will not be able to meet the increasing requirements until lithium-rich layered oxides emerge with beyond-capacity performance. Nevertheless, in-depth understanding of the evolution of crystal and excess capacity delivered by Li-rich layered oxides is insufficient. Herein, various in situ technologies such as X-ray diffraction and Raman spectroscopy are employed for a typical material Li1.2 Ni0.2 Mn0.6 O2 , directly visualizing O- O- (peroxo oxygen dimers) bonding mostly along the c-axis and demonstrating the reversible O2- /O- redox process. Additionally, the formation of the peroxo OO bond is calculated via density functional theory, and the corresponding OO bond length of ≈1.3 A matches well with the in situ Raman results. These findings enrich the oxygen chemistry in layered oxides and open opportunities to design high-performance positive electrodes for lithium-ion batteries.

Quantifying excess deaths related to heatwaves under climate change scenarios: A multicountry time series modelling study

Abstract: BACKGROUND: Heatwaves are a critical public health problem. There will be an increase in the frequency and severity of heatwaves under changing climate. However, evidence about the impacts of clima ...

Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis.

Abstract: Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community-acquired and healthcare-associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class-definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de-escalation or termination of antimicrobial therapy are now important parts of decision-making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

Abstract: The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage However, biliary drainage should be considered if a patient does not respond to initial treatment For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage For severe acute cholangitis, appropriate respiratory/circulatory management is required Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management Free full articles and mobile app of TG18 are available at: http://wwwjshbpsjp/modules/en/indexphp?content_id=47 Related clinical questions and references are also included

Fungal Morphogenesis, from the Polarized Growth of Hyphae to Complex Reproduction and Infection Structures

Abstract: Filamentous fungi constitute a large group of eukaryotic microorganisms that grow by forming simple tube-like hyphae that are capable of differentiating into more-complex morphological structures and distinct cell types. Hyphae form filamentous networks by extending at their tips while branching in subapical regions. Rapid tip elongation requires massive membrane insertion and extension of the rigid chitin-containing cell wall. This process is sustained by a continuous flow of secretory vesicles that depends on the coordinated action of the microtubule and actin cytoskeletons and the corresponding motors and associated proteins. Vesicles transport cell wall-synthesizing enzymes and accumulate in a special structure, the Spitzenkorper, before traveling further and fusing with the tip membrane. The place of vesicle fusion and growth direction are enabled and defined by the position of the Spitzenkorper, the so-called cell end markers, and other proteins involved in the exocytic process. Also important for tip extension is membrane recycling by endocytosis via early endosomes, which function as multipurpose transport vehicles for mRNA, septins, ribosomes, and peroxisomes. Cell integrity, hyphal branching, and morphogenesis are all processes that are largely dependent on vesicle and cytoskeleton dynamics. When hyphae differentiate structures for asexual or sexual reproduction or to mediate interspecies interactions, the hyphal basic cellular machinery may be reprogrammed through the synthesis of new proteins and/or the modification of protein activity. Although some transcriptional networks involved in such reprogramming of hyphae are well studied in several model filamentous fungi, clear connections between these networks and known determinants of hyphal morphogenesis are yet to be established.

Non-Hermitian perspective of the band structure in heavy-fermion systems

Abstract: We analyze a two-dimensional Kondo lattice model with special emphasis on non-Hermitian properties of the single-particle spectrum, following a recent proposal by Kozii and Fu. Our analysis based on the dynamical mean-field theory elucidates that the single-particle spectral weight shows the exceptional points (EPs). Correspondingly, the spectral weight exhibits the band touching, resulting in a structure similar to the Fermi arc. Furthermore, we find an intriguing phenomenon arising from the periodicity of the lattice. The EPs generated by two distinct Dirac points merge and change into a hybrid point, which vanishes as the exchange interaction is increased. Accordingly, the paramagnetic phase in the low-temperature region shows a significant difference from noninteracting fermions: the imaginary part of the self-energy yields the Fermi loop without any defective points.

Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.

Abstract: Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton-proton collisions at s√ = 13 TeV

Abstract: The performance of the missing transverse momentum ( ETmiss ) reconstruction with the ATLAS detector is evaluated using data collected in proton-proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct ETmiss , fully calibrated electrons, muons, photons, hadronically decaying τ-leptons , and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various ETmiss contributions. The individual terms as well as the overall reconstructed ETmiss are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the ETmiss scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2fb-1 .

The neural mechanisms and circuitry of the pair bond.

Abstract: Love is one of our most powerful emotions, inspiring some of the greatest art, literature and conquests of human history. Although aspects of love are surely unique to our species, human romantic relationships are displays of a mating system characterized by pair bonding, likely built on ancient foundational neural mechanisms governing individual recognition, social reward, territorial behaviour and maternal nurturing. Studies in monogamous prairie voles and mice have revealed precise neural mechanisms regulating processes essential for the pair bond. Here, we discuss current viewpoints on the biology underlying pair bond formation, its maintenance and associated behaviours from neural and evolutionary perspectives.

Search for Higgs boson pair production in the γ γ bb¯ final state with 13 TeV pp collision data collected by the ATLAS experiment

Abstract: A search is performed for resonant and non-resonant Higgs boson pair production in the $ \upgamma \upgamma b\overline{b} $ final state. The data set used corresponds to an integrated luminosity of 36.1 fb$^{−1}$ of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess relative to the Standard Model expectation is observed. The observed limit on the non-resonant Higgs boson pair cross-section is 0.73 pb at 95% confidence level. This observed limit is equivalent to 22 times the predicted Standard Model cross-section. The Higgs boson self-coupling (κ$_{λ}$ = λ$_{HHH}$/λ$_{HHH}^{SM}$ ) is constrained at 95% confidence level to −8.2 < κ$_{λ}$ < 13.2. For resonant Higgs boson pair production through $ X\to HH\to \upgamma \upgamma b\overline{b} $ , the limit is presented, using the narrow-width approximation, as a function of m$_{X}$ in the range 260 GeV < m$_{X}$ < 1000 GeV. The observed limits range from 1.1 pb to 0.12 pb over this mass range.

Measurement of the W-boson mass in pp collisions at s=7TeV with the ATLAS detector.

Abstract: A measurement of the mass of the $W$ boson is presented based on proton-proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb$^{-1}$ of integrated luminosity. The selected data sample consists of $7.8 \times 10^6$ candidates in the $W\rightarrow \mu u$ channel and $5.9 \times 10^6$ candidates in the $W\rightarrow e u$ channel. The $W$-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the $W$ boson transverse mass in the electron and muon decay channels, yielding \begin{eqnarray} m_W &=& 80370 \pm 7 \, (\textrm{stat.}) \pm 11 \, (\textrm{exp. syst.}) \pm 14 \, (\textrm{mod. syst.}) \, \textrm{MeV} &=& 80370 \pm 19 \, \textrm{MeV}, \end{eqnarray} where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the $W^+$ and $W^-$ bosons yields $m_{W^+}-m_{W^-} = -29 \pm 28$ MeV.

cGAS drives noncanonical-inflammasome activation in age-related macular degeneration

Abstract: Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin D, interferon-β, and cGAS levels were elevated in the RPE in human eyes with geographic atrophy. Collectively, these data highlight an unexpected role of cGAS in responding to mobile-element transcripts, reveal cGAS-driven interferon signaling as a conduit for mitochondrial-damage-induced inflammasome activation, expand the immune-sensing repertoire of cGAS and caspase-4 to noninfectious human disease, and identify new potential targets for treatment of a major cause of blindness.